ABSTRACT The DNA Sequencing Facility within the Skirball Institute at New York University Langone Medical Center provides sequencing services to about 200 labs and hundreds of scientists in the NYU community. As a core facility, the sequencing lab offers state-of-the-art equipment and expertise, which would be impractical for most individual labs to maintain. We are requesting funds to purchase a Roche Genome Sequencer FLX (GS FLX), developed by 454 Sequencing, a Roche corporation. This pyrosequencing instrument generates over one million unique high quality sequencing reads with an average of 350 to 400 bases pairs in length within a ten hour instrument run time. The total average yield per instrument run is 400 to 500 megabases, and since it is possible to run the instrument multiple times a week, gigabases of useable data can be produced. The instrument supports a wide variety of applications, including de novo pathogen sequencing, metagenomics, target region resequencing, transcriptome sequencing, SNP identification, small RNA analysis, copy number variation, and DNA methylation. The platform would provide the Medical Center with the ability to support ongoing NIH-funded projects at a significantly reduced cost compared to traditional Sanger technologies, with a turn around time that can be measured in days to weeks instead of months to years. Such experiments will greatly increase our understanding of the causes and mechanisms of a number of diseases of the skin, intestinal tract and gastroesophageal tract, such as psoriasis and gastroesophageal reflux disorders, as well as infectious diseases such as malaria and HIV.